Since the inception of WINS, the Bronx/Manhattan site has demonstrated both scientific and operational leadership nationally, and has provided the most data, with the largest retained cohort and the greatest participation in substudies. Dr. Anastos, the Bronx/Manhattan PI, has led the WIHS investigations of natural and treated history both before and after the introduction of HAART. In WIHS III the Bronx team has added to these accomplishments by broadening its scientific focus and markedly increasing its scientific productivity. This was achieved through development of a data analysis team, enhancement of our expertise in metabolic conditions of interest, the addition of a co-Pi with expertise in substance use and hepatitis C, continued support and flexibility for investigations of pathogenesis, and active management of data analysis and manuscript development. In WIHS III the Bronx has produced more papers than any other site in disease progression/response to HAART, metabolic complications, and pathogenesis, the three areas in which we concentrate our scientific expertise. In addition, the Bronx WIHS established an international liaison in WIHS through with a sister cohort in Rwanda. In WIHS IV we propose to continue our operational excellence in data volume, completeness and quality;to develop further our local team's scientific productivity;to provide continued leadership in WIHS scientifically;and to develop further international collaborations in which WIHS can contribute to understanding of important parameters of the international epidemic inwomen.